ATLANTA -- Transgender youth receiving puberty-delaying hormone therapy or gender-affirming hormonal therapy have lower bone mineral density (BMD). This is regardless of whether they were assigned gender at birth.
As patients are exposed to sex steroids hormones for longer periods of time, the problem becomes more severe. Natalie Nokoff, MD presented a cross-sectional study on bone mineral density at ENDO 2022: Atlanta Endocrine Society Annual Meeting last month.
Nokoff and her coworkers are conducting research on bone density as part of a larger body about the long-term effects of gender affirming therapy in children, adolescents and adults. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists -- which effectively block puberty -- were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.
Nokoff, an assistant professor of endocrinology and pediatrics at the University of Colorado School of Medicine in Aurora, stated that "we need more information about the optimal length of treatment using puberty-delaying medication before discontinuation or introduction of hormones gender-affirming."
This study involved 56 transgender teens who were subject to total body dual-energy, x-ray absorptiometry. Patients ranged from 10 to nearly 20 years old. Only 53 percent of the patients were given female sex at birth, which is just over half.
The Z scores, which indicate deviation from age-matched norms were lower than the mean Z scores for transgender males and transgender women, regardless of whether they had used or not GnRH agonists.
Michele A. O'Connell MBBCh, Department of Endocrinology and Diabetes Royal Children's Hospital Victoria, Australia was asked to comment. She stated that the risk of bone fractures is real.
"Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists," said O'Connell. O'Connell referred to several guidelines, including those published by the World Professional Association of Transgender Health (2012) and the Endocrine Society (2017).
Nokoff's study found that the BMD Z score for transgender men was lower than male norms by 0.2 and 0.4 respectively, while female norms were reduced by 0.4. The scores for transgender females were reduced by 0.4 relative the male norms and by 0.2% relative to the female norms.
The Z score of transgender males taking testosterone who had been previously exposed to GnRH antagonists was significantly lower than that of those who took testosterone alone (P =.004). Transgender females who took estradiol only had no difference in Z scores compared to transgender males who were exposed to GnRH agonists.
The Z scores of transgender females and the duration of GnRH antagonist therapy were significantly correlated (P =.005) relative to male norms (P=.029). Z scores did not correlate with the length of treatment with testosterone, estradiol or sex steroids.
There is an increasing number of adolescents and children who are taking gender-affirming or puberty-delaying therapies. While there are not many reliable data, it seems that gender identity exploration has become more popular with increasing social acceptance of gender dysphoria. Nokoff defines this as a feeling of unease in individuals who feel their biological sex is not compatible with their gender identity.
She stated that it was now believed that only 2% of transgender youths identify themselves as such.
Studies that looked at the relationship between adult bone loss and gender-affirming therapy have not produced consistent results. A single-center study that followed 543 male transgender people and 711 female transgender people who had been subject to DEXA scanning prior to beginning hormone therapy showed no significant changes in lumbar bone density (J Bone Min Res. 2018 Dec;34:447-54).
There is increasing evidence that adolescents are at risk of bone loss due to gender-affirming therapies. However, there is not much consensus on how to avoid them. Relevant variables include genetics, diet, and the type, dosage, and duration of gender-affirming treatment.
O'Connell was the first to publish a summary on the pharmacologic management for trans and gender-diverse teens. This summary included many topics, in addition to the risk of bone loss (J Clin Endocrinol Metab). 2022 Jan;107:241-257).
She agrees that children who receive puberty-delaying and gender-affirming therapies should have their bone health monitored. However, she also agrees that there is still little to no clinical evidence.
She stated that long-term follow up studies would be necessary to determine if there was any impact on functional outcomes like fracture risk. She encouraged the use of traditional methods to improve bone health, such as adequate vitamin D intake, weight-bearing exercise, and proper vitamin D intake.
O'Connell and Nokoff have not disclosed any relevant financial relationships.
ENDO 2022: The Endocrine Society Annual Conference.
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